ABSTRACT
Introduction
Catha edulis (Vahl) Forssk. ex Endl. (Celestraceae) is used as a recreational drug on daily basis for its euphoric and psychostimulant effects. It is also chewed by individuals who are on medications, raising the possibility of drug-khat interaction. However, limited data are available in the literature, although clinically significant interactions are expected, as khat contains a complex mixture of pharmacologically active constituents.
Areas covered
It provides an overview of the phytochemistry, pharmacokinetics, pharmacodynamics, and pharmacogenetics of khat based on the literature mined from PubMed, Google Scholar, and Cochrane databases. It also presents a detailed account of drug–khat interactions with specific examples and their clinical significance. The interactions mainly occur at the pharmacokinetics level and particular attention is paid for the phases of absorption and cytochrome P450 enzyme-mediated metabolism.
Expert opinion
Despite the increasing trend of khat chewing with medications among the populace and the potential risk for the occurrence of clinically significant interactions, there is paucity of data in the literature demonstrating the magnitude of the risk. The available data, however, clearly demonstrate that the consequence of drug–khat interaction is dependent on genotype. Genotyping, where feasible, could be used to improve clinical outcome and minimize adverse reactions.
Article highlights
Khat is chewed for its psychostimulant effect and yet can produce many undesirable effects in other parts of the body. However, all effects of khat cannot totally be ascribed to cathinone.
Conversion of the labile and active alkaloid (cathinone) to less active and stable alkaloid (cathine) is possibly mediated by CYP2D6.
Khat interacts with clinically used drugs through different mechanisms, including complex formation, delay in gastric emptying, increasing urinary elimination, inhibition of cytochrome P450 enzymes, and increasing dopamine release.
Khat significantly inhibits CYP2D6 and marginally inhibits CYP2C19 and CYP3A5.
The extent of enzyme inhibition depends on genotype. It is more pronounced in individuals carrying the CYP2D6*1/*1, CYP2C19*2 or *3, CYP3A5*3 or *6, and CYP1A2*1/*1 alleles.
The outcome of inhibition could be development of adverse drug reaction or loss of therapeutic efficacy, depending on the nature of the interacting drugs.
Genotyping could improve clinical outcome and minimize adverse reactions.
Acknowledgments
The authors would like to thank Netsanet Fekadu, Getachew Alemkere, and Wondimagegn Tamiru for their help in identifying and providing information for the present review.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.